Biomarkers Battle for Best Heart Test

Action Points

This is an expert consensus document from the Society for Cardiovascular Angiography and Interventions addressing the consideration of a new definition of clinically relevant MI after coronary revascularization.

The document recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI" and it suggests that CK-MB is better validated as a biomarker than cTn.

The biomarker CK-MB should be preferred over cardiac troponin (cTn) to identify coronary angioplasty-related myocardial injury that predicts later events, a new consensus statement said.

When clinicians switched to cTn from CK-MB, they didn't have a thorough understanding of the prognostic implications of rising levels of cTn following percutaneous coronary intervention (PCI), according to Issam D. Moussa, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues.

Cardiac troponin, for example, can be overly sensitive, resulting in unfounded suspicion that many patients have suffered a clinically relevant myocardial infarction (MI) than the objective evidence would support, they wrote in the paper published online in Catheterization and Cardiovascular Interventions.

The writing committee of the Third (and latest) Universal Definition of MI, published in 2012, noted that the cTn thresholds were "arbitrarily chosen and of uncertain clinical relevance, and not grounded on substantial scientific evidence linking their occurrence to subsequent adverse outcomes," Moussa and colleagues pointed out.

However, in its defense, the Third Universal Definition employed higher thresholds of biomarkers than its predecessor and more stringent criteria for PCI-related MIs, wrote Hani Jneid, MD, of Baylor College of Medicine in Houston, in a commentary along with the publication of the new definition.

The new high-sensitivity assays detect very low levels of cTn, resulting in many false positives, they said.

In fact, the new expert consensus statement, developed by the Society for Cardiovascular Angiography and Interventions (SCAI), recommends against the use of high-sensitivity assays for post-PCI (and post-CABG) MI.

Another cardiac MRI study found the sensitivity, specificity, and positive predictive value of cTn I to rule in or out MI were 100%, 22%, and 19%, respectively. When CK-MB was used, the analogous findings were 60%, 93%, and 60%, respectively, according to Chris Lim, MBBS, from the Oxford Heart Centre in England, and colleagues.

The definition of MI for both biomarkers in the study was levels greater than three times the 99th percentile of the upper reference limit (URL).

To increase the specificity of cTn to equal that of CK-MB (93%), Lim and colleagues said the cTn threshold would need to be 40 times the 99th percentile URL -- however, the sensitivity would not change.

Also of note, the new expert consensus document calls for biomarker assessment before as well as after PCI.

Moussa and colleagues said that cTn may be falsely elevated in 10% or more of patients post-PCI for various reasons including analytical errors or cTn presence due to non-cardiac causes. Also, evidence suggests that pre-PCI cTn elevations correlate better with subsequent mortality.

If possible, two biomarker assessments should be taken within 24 hours of PCI, even if the procedure is uncomplicated. Rarely, however, is even one measurement taken after a uncomplicated PCI, the authors noted.

Current guidelines from the American Heart Association, the American College of Cardiology, and SCAI assign a class IIb recommendation to biomarker assessment following uncomplicated PCI.

Nevertheless, the new consensus document, the authors said, is a first step in addressing the limitations of the current definition of clinically relevant MI.

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